Toxicity from antidepressant agents is considered a common phenomenon. The aim of this study was to estimate the role of intravenous lipid emulsion (ILE) as compared to sodium bicarbonate (Na bicarbonate) as a main line or as an adjunctive therapy for treatment of cardiovascular toxicity induced by concurrent single oral administration of amitriptyline and citalopram in rats. The intoxicated rats were equally divided into three groups. Group1 received a bolus dose of 2mEq/kg Na bicarbonate then by infusion of 0.25ml/kg/min. Group 2 received a bolus dose of 1.5ml /kg of 20% ILE followed by infusion of 0.25 ml/kg/min and increased stepwise to 12.4 ml/kg. Group 3 received Na bicarbonate + ILE by the same pattern and doses. All therapies were injected for 60 min. Mean arterial blood pressure (MAP), heart rate (HR) and electrocardiogram for QRS duration were assessed across all intervals with comparison of pH recordings before and after therapies. The results showed significant improvement of MAP and QRS prolongation after the iv bolus dose, along infusion period and even after 10 min of the follow up. HR was not changed in all groups while pH showed significant improvement after the end of therapies administration in all groups. No significant differences were found between Na bicarbonate and ILE groups while there was a highly significant improvement in Na bicarbonate + ILE group as compared to the other groups. In conclusion, ILE can be used alone or as an adjunctive therapy with Na bicarbonate which is preferred to reverse the cardiovascular toxicity induced by combined antidepressant agents in adult rats.