Objective To explore the correlation between the methylation level of 5-hydroxytryptamine receptor 1A(HTR1A) gene promoter region and severity of symptom in the manic episode patients with bipolar disorder type Ⅰ(BD-Ⅰ). Methods Fifty six manic episode patients with BD-Ⅰ and fifty nine healthy controls were randomly included in the study.The level of HTR1A gene promoter methylation was measured with pyrosequencing technique in both manic episode patients with BD-Ⅰ and the healthy controls.The severity of symptoms was assessed with score of Bech-Rafaelsen Mania Rating Scale(BRMS) in patients with BD-Ⅰ.Pearson correlation analysis was employed to explore the correlation between the serum level of HTR1A promoter methylation and score of BRMS in BD-Ⅰgroup. Results Increased serum level of HTR1A gene promoter methylation was found in manic episode patients with BD-Ⅰ((66.55±10.55)%) compared with that in healthy controls((54.03±8.85)%)(P<0.01). Positive correlation was found between the serum level of HTR1A gene promoter methylation and total score of BRMS in manic patient with BD-Ⅰ(r=0.534, P<0.01). Conclusion The current findings suggest that the serum level of HTR1A gene promoter methylation can be an epigenetic indicator for severity of manic symptom in BD-Ⅰ. Key words: Bipolar disorder; Epigenetics; DNA methylation