Cisplatin (CP) is a ubiquitous antineoplastic medicine that has been recognized to have sever toxic effects on different organs including lungs. Rhoifolin (RHO) is a therapeutic compound with significant pharmacological activities. The present study was designed to evaluate the protective effect of RHO against CP induced pulmonary toxicity. Twenty-four rats were randomly divided into 4 groups: control group, CP treated group (20 mgkg−1), CP + RHO treated group (20 mgkg−1 + 10 mgkg−1) and RHO supplemented group (10 mgkg−1). Following 30 days of administration, our results showed that CP treatment decreased the activity of antioxidant enzymes such as glutathione (GSH), glutathione reductase (GSR), glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD), catalase (CAT) while elevated the level of malondialdehyde (MDA) along with reactive oxygen species (ROS). Furthermore, levels of inflammatory cytokines involving interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and cyclo-oxygenase-2 (COX-2) activity were escalated. Besides, treatment with CP enhanced the activities of apoptotic proteins i.e., Bax, caspase-9 along with caspase-3 while reducing the activity of Bcl-2. Additionally, the histopathological examination revealed significant pulmonary tissue impairments in the CP exposed group. However, RHO treatment considerably (P
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