Background: Previous studies have demonstrated that scorpion venom increases blood levels of some cytokines, including Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) in experimental model of scorpion envenomation in laboratory animals. Objectives: This study aimed to measure circulating cytokines levels in rats after envenomation with Mesobuthus Eupeus scorpion and to compare the findings in rats treated with polyvalent antivenom to evaluate the role of routine treatment in scorpion envenomation. Materials and Methods: For the present research, the venom of Mesobuthus eupeus scorpion was extracted by electric shock and then intraperitoneally injected (1.5 mg/kg) into 2 groups (V: venom group and AV: antivenom group) of 36 Wistar rats each weighing 200 ± 10 g. Additional 36 rats were considered as control group (group C) and were intraperitoneally (ip) injected with 50 μL saline solution. Group AV were injected ip, with polyvalent antivenom 2.5 ml/kg, 30 minutes after envenomation. Heparinized blood samples were collected by heart puncture at different time periods (1,3,6,12,24, 48, and 72 hours) after venom injection for determination of the levels of plasma cytokines, including IL-1α, IL-6, and TNF-α by Ray Biotech specific ELISA kits for rats. Results: IL-1a, IL-6, and TNF-α levels were significantly increased in 3 hours after envenomation in both groups (V and AV), but the intensity of increase in AV group was less than the other group, i.e. moderate elevation of cytokines occurred after treatment with polyvalent antivenom. At next time points, gradually decreasing amounts of cytokines were seen. Conclusions: Our data suggest that using polyvalent antivenom in short time after envenomation could reduce the inflammatory responses related to the systemic changes during the elevation of cytokines in scorpion envenomation.