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Inflammation plays a crucial role in diabetes and obesity through macrophage activation. Macrophage chemoattractant protein-1 (MCP-1), activin-A, and clusterin are chemokines with known roles in diabetes and obesity. The aim of this study is to investigate their possible diagnostic and/or early prognostic values in children and adolescents with obesity and type-1 diabetes mellitus (T1DM). Methods: We obtained serum samples from children and adolescents with a history of T1DM or obesity, in order to measure and compare MCP-1, activin-A, and clusterin concentrations. Results: Forty-three subjects were included in each of the three groups (controls, T1DM, and obesity). MCP-1 values were positively correlated to BMI z-score. Activin-A was increased in children with obesity compared to the control group. A trend for higher values was detected in children with T1DM. MCP-1 and activin-A levels were positively correlated. Clusterin levels showed a trend towards lower values in children with T1DM or obesity compared to the control group and were negatively correlated to renal function. Conclusions: The inflammation markers MCP-1, activin-A, and clusterin are not altered in children with T1DM. Conversely, obesity in children is positively correlated to serum MCP-1 values and characterized by higher activin-A levels, which may reflect an already established systematic inflammation with obesity since childhood.