Objective: The association between urokinase-plasminogen activator (PLAU) gene rs2227564 polymorphism and Alzheimer’s disease (AD) risk has been widely reported across different ethnic populations, with inconsistent results. Thus, we performed a meta-analysis to assess the association between PLAU rs2227564 polymorphism and AD risk. Methods: Fixed or random effect model was used as the pooling method to assess the basis of homogeneity test among studies. Summarized estimation of odds ratio (OR) and 95% confidence interval (CI) were calculated. Heterogeneity among studies was evaluated using Q test and I2. Publication bias was estimated using Harbord’s test. Results: A total of 27 studies (comprising 6100 AD cases and 5718 controls) were included in this meta-analysis. The present meta-analysis showed a significant increased effect of T allele on risk of AD in dominant model (fixed effect model [FEM] OR 1.123, 95% CI 1.025-1.231) and heterozygote comparison (CT vs CC; FEM OR 1.126, 95% CI 1.027-1.235). No publication bias was detected. Conclusion: This meta-analysis showed that T allele of rs2227564 polymorphism in PLAU gene could increase the effects on risk of AD, and this result needs to be confirmed by further studies.