Obesity and aging are associated with adipose tissue (AT) inflammation and a higher risk of chronic diseases. However, the underlying mechanism remains largely unknown. Here, we investigated the effect of HFD-induced obesity on gene expressions of ATM polarization markers and inflammatory cytokines in male rats with different ages and the possible role of AMPK/SIRT1 pathway in mediating this effect. Sixty male wistar rats were divided into young, adult and old-age groups. Rats of each group were either fed standard diet or HFD. The present results revealed that HFD feeding in all age groups resulted in increased body weight, lipids, visceral adiposity and induced hyperglycemia and insulin resistance compared to controls. Findings revealed significant higher AT IL-6 levels and lower IL-10 levels with significant upregulation of CD11c and CD206 mRNA expressions in all age groups. The histological findings showed increased inflammation and presence of crown like structures in adult and old HFD groups. Moreover, the HFD-induced obesity in groups resulted in significant reduction in p-AMPK levels and SIRT1 expression in AT as compared to controls. AMPK and SIRT1 was positively correlated with IL-10 and CD206 and negatively correlated with TG, HOMA-IR, IL-6 and CD11c in obese groups of different ages. In conclusion, HFD- induced obesity in all ages leads to ATMs polarization and increased inflammatory response that may contribute to metabolic dysfunction. In addition, AMPK/SIRT1 pathway is suggested to be a mediator of ATMs polarization. Thus, targeting this pathway may be promising for treating obesity and aging- related diseases.