Background: Diabetes mellitus (DM) could be classified as type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM) and others according to etiology and pathology. Diabetic nephropathy (DN) is one of the most serious complications of DM. YKL-40 is a marker of inflammation and some studies have indicated that DM was related with inflammation. The objective of our study is to perform a systematic review and meta-analysis to confirm the relationship between YKL-40 and DM as well as DN.Methods: Pubmed, Embase, CNKI and Chinese wanfang databases were searched for eligible studies by two independent authors. Studies were included in this meta-analysis if they fulfilled the following inclusion criteria: (1) a study involving the role of YKL-40 in DM (or DN) designed as a case-control study or cohort study; (2) the data of serum YKL-40 levels were available; (3) studies were published in English or Chinese.Results: Twenty-five studies involving 2498 DM patients and 1424 healthy controls were included. Compared with healthy controls, DM patients had significantly higher levels of YKL-40 (DM: SMD=1.62, 95%CI, 1.08 to 2.25, P=0.000; GDM: SMD=2.85, 95%CI, 1.01 to 4.70, P=0.002). Additionally, DM patients with different degree of albuminuria had significantly higher levels of YKL-40 compared with healthy controls (normoalbuminuria: SMD=1.58, 95%CI, 0.59 to 2.56, P=0.002; microalbuminuria: SMD=2.57, 95%CI, 0.92 to 4.22, P=0.002; macroalbuminuria: SMD=2.69, 95%CI, 1.40 to 3.98, P=0.000) and serum YKL-40 levels increased with increasing severity of albuminuria among DM patients (microalbuminuria vs normoalbuminuria: SMD=1.49, 95%CI, 0.28 to 2.71, P=0.016; macroalbuminuria vs microalbuminuria: SMD=0.93, 95%CI, 0.34 to 1.52, P=0.002).Conclusions: DM patients have higher levels of YKL-40 compared with healthy controls. Additionally, levels of YKL-40 are significantly higher in DM patients with different degree of albuminuria than in the healthy controls and the levels of YKL-40 are positively related with the severe degree of albuminuria. Therefore, our current meta-analysis suggests that their sera should be detected for YKL-40, if DM, especially DN, is suspected in patients.