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This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats.The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU,10 mg/kg every 2 weeks for 8 weeks) into the bladder.Pathological examination on the bladder was conducted to confirm the establishment of the model.All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups.In the nicotine groups,the rats were intragastrically administered nicotine at different concentrations (25,15,5 mg/kg respectively)3 times per week for 8 weeks.The mt-p53 expression was detected by the immunohistochemical method.The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma.The positive rate of mt-p53 expression in the 3 nicotine groups (25,15,5 mg/kg) was 75.00％,58.33％ and 41.67％ by the 14th week,respectively,significantly higher than that in the MNU group (33.33％) (all P＜0.05).The mt-p53 expression rate was positively correlated with the medication dose and time (P＜0.05).It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.