De-regulation of adipocytokines synthesis and secretion appears to be involved in the pathogenesis of different metabolic diseases. We assessed a possible association between plasmatic levels of lipocalin-2 (LCN2) and type 2 diabetes mellitus (T2DM), as well as among levels of LCN2 and those of adiponectin, ghrelin, leptin and resistin, in Mexican diabetic patients. Fifty-three healthy individuals and fifty-three with long-term T2DM were included. Measurements from all patients for BMI, fasting glucose, insulin, lipids and adipocytokine profiles were obtained. Comparison of data between the corresponding for diabetic subjects and those of healthy individuals showed significant differences in every anthropometric and metabolic parameter analyzed (P < 0.001). In diabetic subjects, lipocalin-2 and ghrelin plasmatic levels were statistically diminished (P < 0.001) in comparison with the levels registered in healthy subjects. In conclusion, in this study we found that LCN2 plasmatic levels are reduced in Mexican subjects with long-term diabetes and this reduction in circulating concentrations is similar to the one reported for anti-inflammatory adipocytokines, which suggests that lipocalin-2 is somehow involved in insulin resistance and cardiometabolic alterations through an uncharacterized mechanism generated by the inflammation process.