Regardless of toxicity of nanoparticles, cerium oxide nanoparticles (CeNPs) are emerging as a multi-functional agent for biomedical purposes. On the other hand, Organophosphorus pesticides, like malathion, are inevitably found in the environment. The common involving pathway CeNPs and malathion share is oxidative stress. Therefore, we conducted this study to find the possible neutralizing or synergistic effects of CeNPs on oxidative stress responses in malathion-induced toxicity by intraperitoneal (IP) injection. In this experimental study, 40 Wistar male rats with the weight range of 200-250 g were randomly selected and divided into eight groups. Group1 (control, normal saline), group2 (100 mg/kg/day malathion /IP), group3 (15 mg/kg/day CeNPs/IP), group4 (30 mg/kg/day CeNPs /IP), group5 (60 mg/kg/day CeNPs /IP), group6 (100 mg/kg/day malathion+15 mg/kg/day CeNPs /IP), group7 (100 mg/kg/day malathion+30 mg/kg/day CeNPs /IP) and group8 (100mg/kg/day malathion+60 mg/kg/day CeNPs /IP). After 4 weeks of treatment, the levels of lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol molecules (TTM) and activity of catalase (CAT) in lung tissue were measured. All data were analyzed by SPSS V16 and One way ANOVA with Tukey post hoc test. The results demonstrated that CeNPs caused significant increases in LPO and TAC, in a dose-dependent-manner. For TTM level, none of the groups presented any significant change compared to control. Significantly decreased levels of CAT, also, were seen in all treatment groups. Surprisingly, all animals of group 8 died. Worth of noting, groups receiving combined CeNPs and malathion showed severe responses for these parameters. These results discovered that CeNPs induces oxidative stress parameters and ROS production, especially combined with malathion in lung tissue. Groups receiving both CeNPs and malathion displayed synergistic toxic properties. LPO, TAC and CAT seem to be better parameters for measuring CeNPs-induced responses. Further investigations are required to shed light on clear mechanisms involved.