This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene, showing that insulin induces substantial expression and secretion of MCP-1 in both insulin-resistant (IR) 3T3-L1 adipocytes and IR obese mice (ob/ob). MCP-1 is overexpressed in obese mice compared to lean controls, with white adipose tissue being a major source. In vitro studies demonstrate that MCP-1 decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes, suggesting that elevated MCP-1 may contribute to adipocyte dedifferentiation and the pathologies associated with hyperinsulinemia and obesity, including type II diabetes. The findings highlight the role of MCP-1 in the development of insulin resistance and its potential contribution to the increased risk for cardiovascular diseases in obese individuals.This study identifies monocyte chemoattractant protein 1 (MCP-1) as an insulin-responsive gene, showing that insulin induces substantial expression and secretion of MCP-1 in both insulin-resistant (IR) 3T3-L1 adipocytes and IR obese mice (ob/ob). MCP-1 is overexpressed in obese mice compared to lean controls, with white adipose tissue being a major source. In vitro studies demonstrate that MCP-1 decreases insulin-stimulated glucose uptake and the expression of several adipogenic genes, suggesting that elevated MCP-1 may contribute to adipocyte dedifferentiation and the pathologies associated with hyperinsulinemia and obesity, including type II diabetes. The findings highlight the role of MCP-1 in the development of insulin resistance and its potential contribution to the increased risk for cardiovascular diseases in obese individuals.