Abstract: In the study, bifunctional tanshinone IIA nanoparticles (Tan IIA/M-NPs) with both mannose targeting and reactive oxygen species response were prepared by nanoprecipitation using methoxypoly (ethylene glycol)-disulfide bond-poly (lactic acid hydroxyacetic acid) copolymer (mPEG_5k-SS-PLGA_60k) and phospholipid poly (ethylene glycol) mannan (DSPE-PEG_5k-Man) as the carriers, and tanshinone IIA (Tan IIA) as the model drug. The preferred process parameters were obtained through one-way experiments, and the optimal conditions were determined as follows: a drug-to-carrier mass ratio of 1∶12, an oil-to-water volume ratio of 1∶10, a peloxam concentration of 2.0%, a sonication time of 12 min, and a targeting material modification ratio of 10%. the average particle size of Tan IIA/M-NPs was 198.3 ± 2.8 nm, and the polydispersity coefficient. The average particle size of Tan IIA/M-NPs was 198.3 ± 2.8 nm, the polydispersity index (PDI) was 0.224 ± 0.002, the zeta potential was -2.62 ± 0.94 mV, and the encapsulation rate was (94.41 ± 0.36)%. The results of in vitro cellular experiments showed that Tan IIA concentration in the range of 0.1-100 µmol·L^-1, Tan IIA, blank vector and Tan IIA/M-NPs were all biocompatible with each other and had no significant toxicity to macrophages; the uptake efficiency of inflammatory macrophages by mannose-modified Tan IIA/M-NPs was significantly higher than that of the unmodified group; and Tan IIA/M-NPs significantly reduced the secretion level of macrophage inflammatory factors (TNF-α, IL-1β), inhibited NO production, decreased the proportion of M1-type macrophages, promoted the polarization of M2-type macrophages, and decreased the intracellular level of reactive oxygen species. Tan IIA/M-NPs had a good drug-carrying capacity, and could enhance the inhibitory effect of Tan IIA via mannose targeting and ROS-responsive release. The inhibitory effect on myocardial inflammation provides a new research idea for the regulation of inflammation and tissue repair after myocardial infarction treated with tanshinone IIA.