Objective To establish a cisplatin-resistant 4T1 mouse model of triple negative breast cancer. Methods A drug resistant mice model was established with cisplatin (DDP) induction and in-vivo/in-vitro tumorigenic approach. Its resistance characteristics were identified by MTT assay. Changes of drug resistance gene (MDR1, BCRP, MMP7, GST-π) and protein (P-gp, BCRP, MMP7) expression, and phosphorate-Akt and total-Akt protein expression were evaluated by real-time PCR, immunohistochemistry and western blot method, respectively. Small animal live imaging technology was applied to detect tumor growth. Results Resistance fold (RF) of cisplatin-resistant 4T1 mouse model was 12.84. The expression of MDR1, BCRP, MMP 7, GST-π mRNA and P-gp, BCRP, MMP 7 proteins in the resistant mice were higher than that in the non-resistant mice. The result of western blot showed that a statistically higher expression of p-Akt in resistant mice than that in non-resistant mice at protein levels (P<0.01). No significant difference of tumor growth rate was observed between non-resistant and resistant mice(P>0.05). Given same dose of DDP, resistant mice showed lower sensitivity than non-resistant mice significantly (P<0.01). Conclusions We have successfully established a cisplatin-resistant triple negative breast cancer model in mice, which provides a new platform for further study on chemoresistant reversal strategy and individualized clinical treatment of this disease.