BACKGROUND: Common analgesics such as pentazocine are frequently used for the management and treatment of pain in patients suffering from sickle-cell disease in Nigeria. AIM OF THE STUDY: The current study aimed to investigate the toxicological effects of chronic use of pentazocine on the heart of Wistar rats. METHODS: Twenty-eight (28) female albino wistar rats (120 – 160g) were used for the study. They were grouped into four; control group (1ml normal saline) while experimental groups 2, 3 and 4 were given intramuscular administrations of 30 mg/kg, 60 mg/kg, and 90 mg/kg pentazocine (PZ), respectively for a period of 14 days. Heart samples were obtained and analyzed for biochemical parameters such as catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA). Histopathological analyses of cardiac tissues were also carried out and photomicrographs were obtained. A one-way analysis of variance (ANOVA) was used to analyze the differences between the groups using the Statistical Package for Social Sciences (SPSS) version 23.0. RESULTS: The activities of CAT, and SOD in the PZ-treated groups were decreased while that of MDA increased significantly in comparison with the control group (p < 0.05). Histopathologically, there was evidence of elevated mononucleated inflammatory cardiocytes, with increased depositions of fibrous tissues, and hemorrhages in the PZ-treated rat groups. CONCLUSION: Chronic pentazocine use could induce cardiotoxicity in pentazocine-treated rats.