Background: The aim of the present meta-analysis was to investigate the correlation of serum homocysteine (Hcy) concentration and ulcerative colitis (UC) through pooling all the relevant publications. Methods The electronic databases of PubMed, EMBase, Web of Science, Google Scholar, CBM, and CNKI were systematic searched with the text words of homocysteine/Hcy, ulcerative colitis/UC, and inflammatory bowel disease. The correlation between serum Hcy and UC were demonstrated by stand mean difference (SMD) and corresponding 95% confidence interval (95% CI). The publication bias was evaluated by Egger’s line regression test and Begg’s funnel plot. Results After systematic searching the related electronic databases of PubMed, EMBase, Web of Science, Google Scholar, CBM, and CNKI, eighteen publications relevant to serum Hcy and UC were included in the present meta-analysis. The serum Hcy leves were 14.01±2.76 and 10.31±1.59 μmol/L for UC groups and healthy controls respectively with statistical difference (p<0.05). Significant heterogeneity was found (I2=94.5%, p<0.001) among the included studies. Therefore, the SMD was pooled through the random effect model. The pooled SMD was 1.20 (95% CI: 0.89-1.51), indicating that serum Hcy levels were significant higher in UC groups compared to healthy controls with statistical difference (Z=7.52, P<0.001). Egger’s line regression test indicated no publications bias (t=1.45, p=0.17). Conclusion: Serum Hcy levels were usually elevated in UC patients, which indicates that Hcy may play an important role in UC development and may be used as a serological biomarker for UC diagnosis.