Rheumatoid arthritis (RA) is an inflammatory disease characterized by joint inflammation and cartilage erosion, with current treatments often limited by adverse effects. In this study, we explored the use of human dermal fibroblasts (skin cells) expressing a specific microRNA, miR-192, in combination with platelet-rich plasma (PRP) to alleviate RA symptoms. To assess this, we measured the expression of the collagen-producing gene COL1A2 after introducing miR-192 into fibroblasts. RA was induced in rats by injecting complete Freund’s adjuvant (CFA) into the foot pad. The animals were divided into five groups and treated with either methotrexate, PRP, miR-192, or both PRP and miR-192. Paw volume, arthritis scores, and levels of rheumatoid factor and anti-cyclic citrullinated peptide antibodies were measured. Histopathological analysis was performed to evaluate changes in the ankle joint tissue. The results showed that the combination of PRP and miR-192 significantly reduced paw volume, arthritis severity, and antibody levels compared to other groups. The combination therapy also resulted in less infiltration of inflammatory cells and no cartilage damage, in contrast to the other groups. Our findings suggest that combining PRP with miR-192-expressing fibroblasts promotes collagen production, reduces inflammation, and helps prevent cartilage and joint damage in rheumatoid arthritis. This therapeutic approach could offer a new avenue for improving RA symptoms while minimizing side effects associated with existing treatments.