Background/aims: Tenoxicam is a non-steroidal antiinflammatory drug, which has antipyretic and antiinflammatory effects. Though it is known that the major side effect of non-steroidal antiinflammatory drugs is on the gastrointestinal tract and liver, there have been few studies regarding the effects of tenoxicam. In this study, we aimed to investigate whether tenoxicam has a deleterious effect on liver tissue using immunohistochemical staining and biochemical analysis. Methods: A total of 30 male Wistar albino rats were included in this study. Animals were equally and randomly divided into three groups as follows: Group I (Controls), Group II (Injection with 10 mg / kg / day of tenoxicam) and Group III (Injection with 20 mg / kg / day of tenoxicam). At the end of the study, some liver tissue samples were taken and kept in neutral formalin for histological and immunohistochemical evaluation. Liver tissue samples were embedded in paraffin blocks after routine tissue preparation procedures, and were stained with hematoxylin-eosin and immunohistochemical stain. Liver samples taken for biochemical analysis were washed with physiological saline. Thiobarbituric acid reactive substances and superoxide dismutase activity were measured in the obtained supernatants. Results: There were significant structural changes in liver tissues of the tenoxicam-administered groups when compared with the controls. We observed that hepatic (inducible nitric oxide synthase) receptors were increased in the study groups. Furthermore, hepatic superoxide dismutase and malondialdehyde levels were prominently higher in the tenoxicam-administered groups when compared to levels of the control group. Conclusions: Nitric oxide may exert an antioxidative effect against lipid peroxidation to one point at low levels; however, it may also have the opposite effect at higher levels in tenoxicam induced liver injury.