Objective To investigate the mental health status, perceived social support, as well as the relationship between them among middle school students in Wenchuan Earthquake region, so as to provide references for the relevant department to formulate appropriate strategies and intervention measures. Methods A cluster sampling method was adopted to select all 1698 students (excluded the students in Grade 3) as the research subjects from three middle schools in the disaster regions. All students were investigated with self-designed basic information questionnaire, Symptom CheckList 90 (SCL-90) and Perceived Social Support Scale (PSSS) through self-administered questionnaire. Results The overall positive rate on the SCL-90 was 46.3% among 1690 students, of whom 66.6% had mild psychological problems and 26.5% had moderate to severe psychological problems. The positive rate on the SCL-90 and the score for each factor of SCL-90 were statistically higher in the female students than male students (Plt;0.05). Compared with the senior middle school students, the score on the phobic anxiety subscale of the SCL-90 was statistically higher in the junior middle school students (Plt;0.05), while the score on the obsessive-compulsive subscale was otherwise statistically lower (Plt;0.05). With the exception of the hostility subscale, the score on each subscale of the SCL-90 in the urban students was statistically lower than the rural students (Plt;0.05). The median score on the perceived social support subscale was 60.00, with significant differences between the students of different sexes and grades (Plt;0.05). The overall score on the perceived social support subscale was negatively correlated with the SCL-90 score (r= –0.261, Plt;0.05). The score was negatively correlated with the SCL-90 score in the students regarding different sexes, grades and living areas prior to the earthquake (Plt;0.05). Conclusion The middle school students in the disaster regions have prominent psychological problems; perceived social support is helpful to promote the development of their mental health. In conducting psychological intervention, the difference of individuals’ mental health among different student groups should be concerned, so as to carry out targeted counseling and education.