Social media provide users with multi-directional dialogue for creating and sharing health information that can effectively promote the self-management of health. In regard to the ‘greying’ trend in social media, most researchers have studied the health-related social media (HRSM) acceptance status and use behavior of middle-aged and elderly people, and have explored the role of HRSM in this group. However, the continuous participation of users is the key to the successful operation of HRSM, and is an essential prerequisite for the subsequent HRSM behavior habits of middle-aged and elderly people. Therefore, we aimed to explore what motivations drive the first use of HRSM among middle-aged and older adults, and the impact of their perception of HRSM, after personal use, on their intention to use it continually. In the study, we used the partial least squares structural equation model (PLS-SEM) to analyze data collected from online questionnaires. The results showed that a self-protection motivation and a social motivation promoted the initial participation of middle-aged and elderly individuals. In addition, these people experienced deeper levels of perceived usefulness and perceived entertainment after their initial participation. The results also revealed that these two perceptions could positively influence middle-aged and elderly individuals’ intention to continue with their participation. Our findings should help service platforms to better understand the needs of middle-aged and elderly users. This would help researchers and practitioners to gain a more complete understanding of the motivation of middle-aged and elderly people for participating in HRSM, and the related impacts this may have.