Abstract: The objective of the present study was to investigate the tumor promoting effects of nicotine on exocrine pancreas in azaserine-rat model. Two weeks old male Leeds strain rats were given a weekly i.p. injection of azaserine (30 mg kg-1 body weight) for five weeks. The other group was untreated with azaserine and kept as control groups. At the end of five weeks of treatment, rats were divided into four groups each group including 15 rats and exposed to nicotine for six months. At the end of the experiments, the animals were killed, the bodies were weighted and the pancreases were excised and weighted. The pancreases were kept in 10% formaldehit for histological processes. The results of this study showed that exposure of azaserine for five weeks initiated the pancreatic cancer in rats. The standard diet plus nicotine mixture had an inhibitory effect on acinar cells of rat exocrine pancreas. The observed reduction in stereological parameters such as volume of Atypical Acinar Cell Foci (AACF) and mean focal diameter of foci (AACF) was significant (p<0.05) compared to azaserine initiated control rats. The results of the present study do not provide any evidence for that nicotine promotes exocrine pancreatic carcinogenesis in rat pancreas. Nicotine rather seems to be associated with the reduction of AACF that is produced by azaserine injection.