Objective: The mechanism of left ventricular hypertrophy (LVH) in hypertension is complex. This study was to investigate the role of telmisartan in improving myocardial remodeling in hypertensive LVH and explore the potential molecular mechanism. Design and method: Eight-week male Sprague-Dawley (SD) rats were used to establish hypertensive LVH model through abdominal aortic constriction. Telmisartan was intragastrically administered 6weeks after surgery. Cardiac fibroblasts were used in vitro experiments under the treatment of angiotensin II (AngII), leptin or different inhibitors. The cardiac function and myocardial remodeling level were evaluated in rats, and the AngII-AT1R-ROS-ERK1/2-AP-1 pathway, leptin-JAK2/STAT3-TGF-β1/Smad3 pathway, and the metabolism-related parameters of collagen fibers were detected in cardiac fibroblasts. Results: Telmisartan treatment could alleviate left ventricular diastolic dysfunction (Table 1), reduce myocardial local RAAS and leptin level (Table 2), improve myocardial fibrosis and inhibit the activation of leptin-JAK2/STAT3-TGF-β1/Smad3 pathway in hypertensive LVH rats (Figure 1). AngII could increase the expression of leptin and induce AP-1 nuclear transposition in cardiac fibroblasts, and AT1R antagonist telmisartan, ROS scavenger NAC, ERK1/2 inhibitor PD98059 or AP-1 inhibitor SR11302 could inhibit leptin synthesis and secretion induced by AngII (Figure 2). Leptin could induce collagen metabolic disorders in cardiac fibroblasts, which could be partly restored by JAK2 inhibitor AG-490, STAT3 inhibitor S3I-201 or telmisartan. Telmisartan could reduce leptin synthesis and secretion as good as leptin antagonist, and improve collagen metabolism disorder induced by AngII better than leptin antagonist (Figure 3). Telmisartan could increase the expression of PPAR-γ to almost 3-fold of the control group. When pretreated with PPAR-γ inhibitor GW9662, telmisartan couldn’t restore the collagen metabolic disorders and the increased expression of P-STAT3 stimulated by leptin (Figure 4). Conclusions: Telmisartan can improve myocardial remodeling in hypertensive LVH rats via two ways: one is inhibiting leptin autocrine induced by local AngII as AT1R antagonist, the other is inhibiting leptin downstream signaling molecular STAT3 phosphorylation as PPAR-γ agonist (Figure 5). These findings demonstrate the crosstalk between myocardial local RAAS and leptin, and reveal a new molecular mechanism of telmisartan in improving myocardial remodeling in hypertensive LVH.