Chloroquine, an aminoquinoline, which was formerly the first-line drug for the treatment of malaria for many years until it was discouraged due to drug resistance strains of malaria parasite has been re-purposed for the treatment of many infectious, immunologic and inflammatory disorders because of its inherent property. This study evaluates the possible therapeutic potential of chloroquine, its combination with steroid in the treatment of acrylamide-induced nephropathy. Five groups of male Wistar rats were used for the study: Group 1 rats were used as the untreated control; group 2 rats were intoxicated with oral 2 mg/kg/day of acrylamide (ACR) for 14 days. Following the induction, Groups 3, 4 and 5 rats were treated with chloroquine (25 mg/kg/day), chloroquine + prednisolone (25 mg/kg/day + 5 mg/kg/day) prednisolone (5 mg/kg/day) for 28 days respectively. Urine volume, protein estimation and highly sensitive biomarkers of renal injury (cystatin C, KIM-1, urea, and creatinine) were assessed. In addition, inflammatory and complement factors were also evaluated. Results showed that chloroquine, and its combination with prednisolone attenuated the biochemical parameters of kidney injury as well as reversing inflammation and complement activation. Furthermore, the anti-apoptotic potential of this drug was demonstrated by immunohistochemistry analysis, which revealed BAX down-regulation, caspase 3, and 9 expressions. Also, ACR-induced histological changes were significantly reversed by this drug. Thus, highlighting the promising therapeutic potential of chloroquine in mitigating ACR-induced nephropathy, which was probably mediated via anti-inflammatory and anti-apoptotic mechanisms.