High density lipoprotein (HDL-C) is inversely correlated with the incidence of coronary artery disease. One of the protective effects of HDL-C against atherosclerosis is via reverse cholesterol transport (RCT) pathway. RCT pathway is critical for the transfer of excess cholesterol from peripheral cells back to liver for subsequent catabolism and exertion. The initial step of RCT is depending on ABCA1 to efflux the cholesterol from cell to lipid-poor Apolipoprotein AI. PURPOSE: To investigate the time course (immediately, after 2 hours and after 24 hours) expressions of ABCA1 in response to acute endurance exercise. Method: All experiments in this study were conducted acoording to the policy of NIH guidelines regarding the use of animals. Twenty male rat (12-14 years old, weighting 200-220 gr) divided into two groups (control n=10 and exercise n=10). Animals were kept in the Central Animal House, School of Medical Sciences of Tarbiat Modares University. Light was controlled using a 12 hour light-dark cycle. Temperature was 22±1.4° C and humidity was 55.6±4.0%. Animals were fed a pellet rodent diet add libitum and had free access to water. Exercise groups were given treadmill running for 2 hours at the intensity of 18 m/min. The first group of rats (control n=3, Exercise n=3) were sacrified immediately after exercise. The second group of rats (control n=3, exercise n=4) sacrified after 2 hours and third group (control n=3, exercise n=4) sacrified 24 hours after the end of exercise. The rat's liver excised immediately and frozen in liquid nitrogen for extraction of mRNA. The liver expression of ABCA1 was determined by semi-quantitative PCR and the levels of ABCA1 mRNA were expressed as a ratio of signal intensity for the Beta actin gene. RESULTS: The results of group 1 didn't show any significant differences between the liver expression of ABCA1 in control and exercise rats (26.74±7.7 vs. 25.9±4.8, P=0.880). But the significant different was observed between the control and exercise rats of group 2 (36.81±2.5 vs. 45.85±3.7, P=0.041) and group 3 (29.81±9.9 vs. 73±4.8, P=0.021) in response to acute endurance exercise. CONCLUSION: This is the first study investigating the effect of acute endurance exercise on the expression of ABCA1. The results clearly show the liver expression of ABCA1 in response to acute endurance exercise after 2 and 24 hours of exercise session but not immediately after exercise. This gene expression suggests that even one exercise session can trigger the reverse cholesterol transport pathway which can lead to prevention of atherosclerosis. This study was supported by Unversity of Tehran.