Abstract: Background and Objective: In diabetes management, hypoglycemia unawareness (HU) syndrome is the result of frequent incidences of hypoglycemic episodes due to intensive glycemic control. The HU leads to a longer duration of hypoglycemia due to the absence of alerting symptoms, causing several complications in the cardiovascular system, such as hypertension and cardiac injury. In the current study, the role of carnitine was evaluated in the improvement of hematological parameters and prevention of cardiac PRR and caspase-3 expression in hypoglycemia-induced cardiac hypertrophy. Materials and Methods: A group of male Wistar albino rats (n = 15) was divided into 5 groups (n = 3) and treated with insulin glargine (InG) at doses 0, 10, 15, 20 and 25 U/kg/day for finding the optimal dose to provide sustained hypoglycemic condition. Second group (n = 20) was divided into 4 groups (n = 5) and treated with saline, InG 20 U/kg/day, InG+D-carnitine (InG+DC) for carnitine depletion and InG+acetyl-L-carnitine (InG+ALCAR) for carnitine supplementation. Results: The present study demonstrated that hypoglycemia-induced leukopenia was exaggerated with carnitine deficiency, whereas, white blood cells decreased from 6.93±1.58×103 in InG group to 5.47±0.77×103 in InG+DC group as all compared with control group (12.62±1.45×103). The ALCAR ameliorated the hematological parameter and treated hypoglycemia-induced leukopenia. In the heart, (pro)renin receptor (PRR) and caspase-3 expression were upregulated during hypoglycemia and exaggerated with carnitine deficiency leading to cardiac hypertrophy. The ALCAR prevented hypoglycemia-induced cardiac hypertrophy might be through the down regulation of PRR and caspase-3 expression. Conclusion: Carnitine has an important role in the prevention of hypoglycemic complications, such as leukopenia and cardiac hypertrophy, through the regulation of PRR and caspase-3 in cardiac tissues.