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Objective To investigate the predictive role of serum C1q tumor necrosis factor related protein 12（CTRP12） level in patients with type 2 diabetes mellitus（T2DM） and diabetic nephropathy（DN）. Methods Using a cross-sectional, single center study design, 60 patients with T2DM（T2DM group）, 70 patients with T2DM and DN（T2DM+DN group）, and 60 healthy subjects（control group） admitted to Haikou Peoples Hospital from January 2020 to December 2020 were selected. According to urinary albumin excretion rate（UAER）, patients in T2DM+DN group were divided into microalbuminuria DN subgroup（38 cases） and macroalbuminuria DN subgroup（32 cases）. The level of serum CTRP12 was measured by enzyme-linked immunosorbent assay. ROC curve was used to evaluate the diagnostic efficacy of serum CTRP12 in T2DM and DN. Results The level of serum CTRP12 in macroalbuminuria DN subgroup was（348.65±53.24）pg/mL, that in microalbuminuria DN subgroup was（472.61±68.59）pg/mL, that in T2DM group was（455.81±84.62）pg/mL, and that in control group was（568.61±105.35）pg/mL, there was significant difference between groups（P<0.01）. The low level of serum CTRP12 was a risk factor for T2DM and DN（P<0.05）. The area under the curve of serum CTRP12 level in the diagnosis of T2DM and DN was 0.844（95%CI: 0.801-0.906）, the best predictive value of serum CTRP12 was 418.26 pg/mL, the sensitivity was 81.89%, and the specificity was 74.55%. Conclusion The level of serum CTRP12 decreased significantly in patients with T2DM and DN. The decrease of serum CTRP12 level may have some predictive value for T2DM patients with DN.