Objective To study the protective effect of various proportions of Scutellariae Radix-Forsythiae fructus in an acute pneumonia mouse model induced by lipopolysaccharide (LPS). Methods The Scutellariae Radix-Forsythiae fructus composition with various compatibility ratios was prepared by the heating reflux method . In total, 144 healthy KM mice were randomly divided into 12 groups ( normal control, model, dexamethasone positive drug, and nine groups of Scutellariae Radix-Forsythiae fructus at various proportions) with 12 mice in each group. Normal control and model groups were administered the same amount of normal saline and the other groups were administered corresponding drugs for 7 continuous days. On day 8, except for the normal control group, mice in other groups were treated with LPS (10 mg / mL) by dripping a solution into the nasal cavity to establish the acute pneumonia model. Samples were collected quickly at 6 hours after modeling. The protective effects of various proportions of Scutellariae Radix-Forsythiae fructus in the acute pneumonia mouse model were evaluated by clinical signs, average daily weight gain, feed intake, the viscera index, serum TNF-α, IL-1β and IL-6 contents, blood routine index, lung histopathological observation, and lung injury histopathological score. Results After modeling, the survival rate of mice in each group was 100%. The normal control group had normal clinical signs, breath sounds, and a sensitive reaction. Mice in the model group were unresponsive and huddled together with rales in the lungs detected by auscultation. Compared with the model group, the overall situation of the various administration groups was better. In particular, the Scutellariae Radix-Forsythiae fructus combination groups (1 ∶ 1, 2 ∶ 3, 1 ∶ 2) showed more activity and sensitive reactions. No significant differences were observed in daily body weight increase, daily feed intake, or kidney, liver, spleen, and thymus indexes (P> 0. 05). Compared with the normal control group, the lung index, serum contents of TNF-α, IL-1β and IL-6, blood biochemical indexes, and histopathological score of lung tissue injury were significantly increased in the model group ( P< 0. 01 or P< 0. 05) . The alveolar wall had significantly thickened, SFTPC protein expression in alveolar and interalveolar regions of lung tissue was significantly increased, and a large number of cells expressed SFTPC protein. Compared with the model group, the heart index of the Scutellariae Radix-Forsythiae fructus combination groups (3 ∶ 1, 3 ∶ 2, 2 ∶ 1, 1 ∶ 3, 3 ∶ 0, 0 ∶ 3) , the lung index of the Scutellariae Radix-Forsythiae fructus combination group ( 1 ∶ 2) , and the serum TNF-α, IL-1β And IL-6 content, blood routine index content of the Scutellariae Radix-Forsythiae fructus combination groups (1 ∶ 1, 2 ∶ 3, 1 ∶ 2) , lung tissue injury scores of the Scutellariae Radix-Forsythiae fructus combination groups ( 3 ∶ 2, 1 ∶ 1, 2 ∶ 3, 1 ∶ 2) were significantly decreased (P < 0. 01 or P < 0. 05) . The lung pathology of mice in the four Scutellariae Radix-Forsythiae fructus groups (3 ∶ 2, 1 ∶ 1, 2 ∶ 3, 1 ∶ 2) was reduced significantly, the expression level of SFTPC protein in the alveolar and interalveolar regions of lung tissue was reduced significantly, and the number of positive cells was low. Conclusions Combination of Scutellariae Radix-Forsythiae fructus(1 ∶ 1, 2 ∶ 3, 1 ∶ 2) has a significant protective effect on LPS-induced acute pneumonia.