BACKGROUND: Observational studies suggested that tobacco smoking was associated with diabetic nephropathy (DN). However, the results were conflicting and inconsistent. In the study, we performed a meta-analysis to assess the relationship between tobacco smoking and the development of DN. MATERIALS AND METHODS: We searched in PubMed, Embase, Web of Science and the Cochrane Library (CENTRAL) from database inception until Mar 8, 2018, and updated our search on May 1, 2018. We screened the reference lists of the retrieved articles. Only original prospective cohort studies which have investigated the association between smoking and DN incidence or its progression were included. Pooled HRs and 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: A total of 9 prospective cohort studies were identified, including more than 203337 participants. Compared with those of no smoking, smoking participants increased the risk of developing DN (HR = 1.07, 95% CI: 1.01-1.13, P = 0.01). The subgroup analysis showed that the current and total smoking may increase the risk of DN, but these results did not reach statistical significance (current: HR = 1.69, 95% CI = 0.79-3.64, p = 0.17; total: HR = 1.17, 95% CI = 0.97-1.41, p = 0.10), whereas former smoking significantly increased the risk of DN (HR = 1.04, 95% CI = 1.03-1.05, p<0.001). Compared with no-smokers, smokers showed an elevated risk of developing DN (HR = 1.05; 95% CI, 1.00-1.11, P = 0.05). In patients with T2DM, those who smoked were at an increased risk of developing DN, as compared to those who had never smoked (HR = 1.05; 95% CI, 1.00-1.11, P = 0.05). However, compared to no smoking, smoking did not increase the risk of DN development in patients with T2DM (HR = 1.15; 95% CI, 0.9-1.47, P = 0.25). Univariate and multivariate meta-regression did not find any confounding factors. No publication bias was found in the meta-analysis. CONCLUSIONS: The present study highlighted that smoking was an independent risk factor for DN, especially in patients with T1DM. This is the first meta-analysis of prospective cohort studies to discuss the relationship between smoking and DN.