Malarial infection causes apoptosis in hepatocytes. However, it is not known if co-administration of antimalarial drug with rutin will reverse the apoptotic effects of malarial infection. Plasmodium berghei-infected mice were assigned into groups as follows: groups Ito III were treated with the vehicle (Parasitised Untreated, PU), 10 mg/kg body weight of Artesunate-Mefloquine (AM) and Dihydroartemisinin-Piperaquine (DP) respectively. Groups IV to VII were treated with AM, DP but co-administered with 100, 200 mg rutin/kg body weight while groups VIII and IX received rutin (100 and 200 mg/kg body weight). Liver mitochondrial Permeability Transition (mPT) and ATPase (mATPase) were determined spectrophotometrically. Caspases 3 and 9 were assayed using ELISA while the levels of bax, cytochrome c release (CCR), p53 and bcl-2 expressions were assayed immunohistochemically. The mPT pore opening fold of 5 (PU), 16 (AM), 14 (AM + 100 mg rutin/kg body weight), 9 (AM + 200 mg rutin/kg body weight), 4(DP), were observed relative to calcium (24) while DP, rutin and their combinations did not open the pore. AM and DP significantly increased caspases 3 and 9 activities, enhanced mATPase activity but co-treatment with rutin (100 mg/kg) decreased these effects significantly. AM + rutin (100 mg/kg body weight) significantly decreased bax, p53, CCR and increased bcl-2 expression. The results showed that supplementing malarial treatment with rutin decreased apoptosis suggesting that rutin supplementation can minimise apoptosis in malarial infection. (C) 2019 Elsevier Inc. All rights reserved.