Angiotensin III (Ang III) is one of the N-terminal angiotensin debasement results of Angiotensin II (Ang II), which imparts a portion of its properties to Ang II, including chemotaxis and creation development factors and chemokines. Ang III indicated comparable capacities to Ang II. The two peptides partake in the cardiovascular (CV) and renal capacities, animating the creation of aldosterone and diminishing renal bloodstream and renin discharge circulatory strain. Angiotensin receptor blockers (ARB) drugs are used for cardiovascular diseases (CVD), their action is by blocking the angiotensin type 1 receptor (AT1R) and the angiotensin type 2 receptor (AT2R). The renin-angiotensin system (RAS) and AT1R inside the mind are likewise engaged with the control of resting metabolic rate and pulse. Leptin (LEP) is a protein encoded by the ob quality communicated in adipocytes. It appeared to connect with fat mass and body weight in ordinary and fat, contributing to controlling the resting metabolic rate and blood pressure through its actions in the arcuate nucleus. This study was designed to investigate the efficacy of ARB's drug on the serum Ang III and the LEP levels in rabbits and to find out the correlation between the serum Ang III and LEP. Forty Oryctolagus cuniculus rabbits were divided randomly to four groups; GI: Losartan 0.7 mg /kg/day, GII: Telmisartan 0.6 mg /kg/day, GIII: Candesartan 0.1 mg /kg/day, and GIV: Placebo. The groups were treated once daily for 10 days, pre and post serum levels of Ang III and LEP were assessed, also estimation of the macroscopic and histopathological changes. Losartan, Telmisartan, and Candesartan groups showed a highly significant decrease in the serum levels of Ang III and LEP compared to baseline. The rabbit's weight and food consumption showed a nonsignificant slight decrease (P=0.06). The observed protective effects of Losartan, Telmisartan, and Candesartan in end organs, such as the heart, liver, and kidneys showed no histopathological changes. There was a highly significant strong positive correlation between Ang III and rabbit's weight, also with food consumption, while LEP showed a weak, non-significant positive coefficient correlation (r) to weight & food consumption. There was a weak positive correlation between serum Ang III and LEP (r=0.047, P=0.06). In conclusion, Losartan, Telmisartan, and Candesartan significantly suppressing RAS activity may be via its effect on Ang III and LEP levels as another mechanism of action for their efficacy as the CV medication.