Triptolide (TP, an active ingredient from Tripterygium wilfordii) demonstrates significant efficacy in treating rheumatoid arthritis, but its low bioavailability and multi-organ toxicity limit its application. Herein, we developed a PEGylated retinoate self-assembled nanomicelles (FA-TP@VA NPs) modified with folic acid (FA) for inflammatory macrophage-targeted delivery of TP. FA-TP@VA NPs showed an appropriate size (192.70 ± 4.37 nm), good physical stability and high drug loading (79.83 ± 5.11 % for retinoate prodrug and 6.78 ± 0.13 % for TP). FA-TP@VA NPs exhibited high cellular uptake in M1 macrophages via folate-receptor pathway, thereby inhibiting their growth. Compared with TP, FA-TP@VA NPs could effectively inhibit synovitis and erosion of bone and reduce swelling and deformation of paws by downregulation of the levels of IL-1β, IL-6, and TNF-α. In ICA mice, FA-TP@VA NPs could enhance drug-specific enrichment in inflamed joints, effectively suppress hepatic oxidative stress and reduce systemic toxicity induced by TP. Overall, FA-TP@VA NPs are a facile, carrier-free, and promising strategy for the precise treatment of rheumatoid arthritis and synergetic attenuation of side effect.