The aim of this study is to investigate the protective effects of Quercetin (QCT) on Hydroxychloquine (HCQ)-induced myocardial affection in rats. HCQ has been found to produce toxic effects including cardiac manifestation. Adding QCT to HCQ ameliorates its effects and prevents cardiac manifestations. For this purpose, eighty adult male rats were divided into four groups (n = 20). Group 1 (control) and group 2 (QCT-treated). Group 3 (HCQ treated) received 20 mg/kg of HCQ and group 4 (QCT + HCQ treated) received quercetin (50 mg/kg; orally) combined with HCQ for 4 weeks. Cardiac troponin-I and oxidative markers (Malondialdehyde (MDA), and total serum antioxidant) were estimated in serum. In addition, histopathological and morphometric changes of the rat heart were assessed. The HCQ treated group showed increased serum levels of cardiac troponin-I, MDA and decreased serum levels of total antioxidant. Pathological picture of myocardial hypertrophy and degeneration together with depleted cardiac tissue expression of troponin T were also observed. The characteristic features were presence of whorled myelin bodies and curvilinear bodies by EM examination. These parameters improved better in the group receiving combination of QCT together with HCQ. So, Adding QCT to HCQ could be prophylactic measure against its cardiotoxic effect compared with HCQ treatment alone.