In this study, we investigated the protective effect of pentoxifilline (PTX) on smoking-induced damage in rat kidney tissues. Twenty-seven male Wistar rats were used in the study. Animals were divided into three equal groups as follows: Group 1: control group with only normal saline (NS; 0.9% NaCl) injection for 8 weeks; Group 2: cigarette smoking and NS injection for 8 weeks; and Group 3: cigarette smoking and PTX injection for 8 weeks. The rats were sacrificed after 8 weeks and their kidneys were excised for histopathological analysis. Serial paraffin sections (5 mm) of the kidneys were cut and stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS). The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method was used to assess apoptosis. Glomerular diameters, glomerular cell number and proximal tubule cell numbers were compared between the groups. Our results showed that PTX treatment prevented negative effects of smoking in rat kidneys. There was a statistically significant difference in all assessed parameters between Group 2 and other groups (p < 0.05). In conclusion, our study shows that PTX treatment is effective in preventing the negative effects of cigarette smoking on kidneys by inhibiting cell damage with its antioxidant properties.