Attention has recently focused on mitochondrial-mediated apoptosis as a signalling pathway that is disrupted during carcinogenesis. The chemopreventive effects of dietary phytochemicals can be explored in order to combat conditions emanating from dysregulation of mitochondria-mediated apoptosis. This study aims to investigate the effects of Cajanus cajan on the opening of the mitochondrial membrane permeability transition pore, ATPase activities, inhibition of lipid peroxidation, liver enzyme activities and immunohistochemical expression of apoptotic biomarkers in rat liver. The leaves of Cajanus cajan were extracted with methanol to obtain the methanol extract of Cajanus cajan (MECC) and different concentrations: 10, 30, 50 and 70 µg/mL were used for in vitro assays. Eighteen male Wistar rats (150± 2.00 g) were assigned into three groups of six animals each and orally treated with corn oil (control), 100 and 200 mg/kg MECC. The rats were treated daily for thirty consecutive days and animals were sacrificed by cervical dislocation. The mitochondrial membrane permeability transition (MMPT) pore, ATPase activity and inhibition of lipid peroxidation were determined spectrophotometrically. Caspase 3, caspase 9 and cytochrome C release were determined by immunohistochemistry. In vitro, the MECC induced pore opening at higher concentrations of the extract. Similarly, enhancement of ATPase activities was also observed. In the in vivo studies; the MECC induced opening of the MMPT pore at 200 mg/kg bwt. On the assessment of the serum transaminases there was a significant increase in the activities of AST and ALP and caspase 3, caspase 9 and cytochrome C release were activated significantly Several chemical constituents were identified by GC-MS. Cajanus cajan induced mitochondrial-mediated apoptosis via the induction of mitochondrial membrane permeability transition with the eventual release of cytochrome C and therefore could be useful in conditions of downregulated apoptosis such as cancer