Aim The aim of this study was to investigate how perceived social support and self-rated health together could mediate the relationship between pain and depression among Chinese nursing home residents with pain. Methods The study was conducted in 38 nursing homes in 13 cities in China. A convenience sample of 2154 older adults responded to the questionnaire survey. A mediation analysis was performed on the data of 990 participants with pain. The data were collected by a questionnaire consisting of socio-economic and demographic characteristics, the Geriatric Depression Scale-15, the Multidimensional Scale of Perceived Social Support, Self-rated Health Scale and the Numerical Rating Scale of pain. The sample was subdivided by sex. Descriptive analysis,t-tests, chi-squared tests, Mann-WhitneyU-tests, Spearman correlation analyses and the bootstrap method were used to analyze data. Results The prevalence rate of pain and depression among nursing home residents were 46.0% and 20.7% respectively. Pain, perceived social support and self-rated health were all significantly correlated with depression (r= 0.217,P < 0.01;r= -0.216,P < 0.01;r= 0.385,P < 0.01, respectively). Perceived social support and self-rated health independently and in series partly explained the relationship between pain and depression. Conclusions The results of the study showed that pain was associated with low perceived social support first, and then poor self-rated health, which was in turn related to the development of depression among nursing home residents with pain. For nursing home residents, perceived social support and self-rated health as an internal resource can affect the ability to overcome the suffering of pain and reduce the level of depression.Geriatr Gerontol Int 2020; center dot center dot: center dot center dot-center dot center dot.