Post anesthesia shivering which happens in some patients during recovery time after general anesthesia is followed by central hypothermia and peripheral vasoconstriction. In this study, the effect of opioidergic/nitrergic systems were determined on post anesthesia shivering in rat. Animals were cooled gently on a cold surface with indirect contact with a mixture of ice and water. Animals were treated with saline; methadone (a full opioid agonist, 10 mg/kg); naltrexone (an opioid receptor antagonist, 10 mg/kg); L-NAME (a nonselective nitric oxide synthase (NOS) inhibitor, 10 mg/kg). The core body temperature and the frequency of basal state- and post anesthetic-shivering were recorded using a stainless steel rectal probe (MLT-1403, AD Instruments®) and electromyography (EMG) electrodes connected to Animal Bio Amp (FE136, AD Instruments®) signal conditioner, respectively. Methadone administration reduced the frequency of shivering after anesthesia, while injection of naltrexone and L-NAME increased post anesthetic shivering compared to vehicle group. Co-administration of L-NAME and methadone showed a significant decrease the frequency of post anesthetic shivering. Furthermore, the temperature of shivering onset was reduced following methadone administration, which was blocked by injection of both naltrexone and/or L-NAME. To conclude, the findings of this study revealed the protective impact of methadone on post anesthesia shivering-induced with hypothermia dominated to nitrergic pathway effects in rat