Objective To investigate the effects of passive smoking in adult female rats on behavior and expression of collapsin response regulatory protein 1 (CRMP1) and death-related protein kinase 1 (DAPK1) in the cerebral cortex of offspring. Methods Eighteen 8-week-old healthy female SD rats were randomly divided into the passive smoking group (n= 9) and control group (n= 9). The passive smoking group was treated with smoke to establish the passive smoking model, whereas the control group was treated normally. After 1 month of smoking, female rats were mated with males and continued smoking until delivery. Offspring (F1 generation) of passive smoking and control groups were evaluated by an open field test, rotary rod fatigue test, and Morris water maze test. These animal behavior tests were conducted to analyze the effects of passive smoking on anxiety, exercise tolerance, and spatial learning and memory abilities of the offspring. Moreover, CRMP1 and DAPK1 protein expression in cerebral cortex tissues of offspring was detected by Western Blot at various developmental stages (0, 7, and 21 days and 4 weeks ( adult)) after birth. Results The open field test showed that the total movement distance and average movement speed of the F1 generation in the passive smoking group were significantly increased in the total area ( P< 0. 05), and the number of entering the central area, and the movement distance and residence time in the central area were significantly increased compared with those of the control (P< 0. 05). The rotary rod fatigue test showed that the sustained movement time and movement distance of the F1 generation in the passive smoking group were significantly reduced compared with those in the control group (P< 0. 001). The Morris water maze showed that escape latency of the F1 generation had no significant difference between passive smoking group and control groups, but swimming speed was significantly decreased in the passive smoking group (P< 0. 001). Compared with the control group, the proportion of time and time of the F1 generation entering the target quadrant in the passive smoking group were significantly decreased (P< 0. 05), and the swimming speed and total swimming distance were also decreased significantly (P< 0. 01). Additionally, Western Blot showed that CRMP1 and DAPK1 protein expression in offspring of the passive smoking group was significantly lower than that of the control group at 0, 7, and 21 days. Conclusions Passive smoking in parental female rats promoted anxiety, reduced exercise tolerance, and impaired spatial memory of offspring, which may be related to regulation of CRMP1 and DAPK1 expression in the brain tissue of offspring.