Purpose: Histamine has multiple biological functions and its immunomodulatory actions are not fully understood. In the current study, we investigated the effect of cimetidine, which is a histamine-2 receptor antagonist, on the progress of transplanted Lewis lung cancers using a mouse model. Methods: A piece of Lewis lung cancer weighing 15 mg was transplanted into the subcutaneous space on the back of each C57BL/6 mouse. Mice were randomized into a no-treatment control group (CO) or one of two treatment groups. In the treatment groups, 16 mg/kg/day (LD) or 160 mg/kg/day (HD) of cimetidine was orally administered from one week before the day of transplantation to the time of sacrifice. Subcutaneous tumors and lungs were excised on the 28th or 42nd post-operative day. Results: The mean vascular densities of the subcutaneous tumors on day 28 were 55.7± 23.9/mm² in CO, 88.0± 16.3/mm² in LD and 122.6± 16.9/mm² in HD (p< 0.05; CO vs. LD or HD, LD vs. HD). On day 42, mean weights of the subcutaneous tumors and the numbers of metastatic lung tumors were 6.0± 2.1 g in CO, 7.9± 1.2 g in LD and 10.0± 1.9 g in HD (p< 0.05; CO vs. HD), and 7.5± 6.0 in CO, 17.0± 3.0 in LD and 19.8± 7.4 in HD (p< 0.05; CO vs. HD), respectively. Conclusions: These results suggest that cimetidine dose-dependently enhances the angiogenesis, growth and metastasis of surgically transplanted Lewis lung cancer in a mouse model of this type.