Local precision therapy for osteoarthritis (OA) still faces dual challenges of low delivery efficiency and high toxicity. This study constructed a triptolide liposome microneedles (TP-Lip-MNs) delivery system. TP liposomes (TP-Lip) were prepared by the thin-film dispersion-ultrasonication method, and the microneedle preparation process was optimized via microneedle mold casting-centrifugal filling-drying technology. The final TP-Lip-MNs exhibited a drug loading content of 63.49 μg per needle, a single-needle mechanical strength of 0.9 N, and a peak drug release at a skin depth of 120 μm. In the pharmacokinetic (PK) study, a quantitative analysis method for TP in rat knee joint microdialysate was established using microdialysis sampling combined with LC-MS/MS. The results showed that the area under the curve (AUC_{0-8 h}) of the TP-Lip-MNs group was 156.80 ± 37.04 ng·h·mL^-1, 2.3-fold higher than that of the TP-Lip group (68.31 ± 5.92 ng·h·mL^-1), and the peak concentration (C_max) was (66.35 ± 18.59 ng·mL^-1), 3.0-fold higher than that of the TP-Lip group (22.49 ± 2.36 ng·mL^-1), significantly enhancing the drug diffusion and absorption rates of TP in the knee joint. In the pharmacodynamic (PD) evaluation using a sodium monoiodoacetate-induced rat OA model, TP-Lip-MNs inhibited inflammation-induced bone hyperplasia as demonstrated by knee swelling rate and CT imaging. The treatment group showed a significant decrease in IL-1β, IL-6, and TNF-α levels after administration, further verifying the anti-inflammatory effect of TP. Serum biochemical indices (ALT, AST, BUN, CRE) confirmed its good biosafety. This study provides an innovative and translationally potential solution for local OA therapy through a "model-delivery-PK-PD" closed-loop design. The animal experiments were approved by the Ethics Committee for Animal Experiments of Tianjin University of Traditional Chinese Medicine under the ethical review number TCM-LAEC2024125g1009.