Background: Folic acid is a targeting ligand for inflammatory tissues since activated macrophages in inflammation overexpress folate receptor. Objective: The aim of this study was to investigate folic acid-modified solid lipid nanoparticles containing carbon monoxide releasing molecule-2 (FA-CORM-2-SLNs) for targeted delivery of carbon monoxide to macrophages. Materials and Methods: FA-CORM-2-SLNs were prepared by nanotemplate engineering technique with palmityl alcohol as a solid lipid and Tween40/Span40/Myrj S40 as a surfactants mixture. The physical properties of FA-CORM-2-SLNs were characterized in terms of particle size, polydispersity index, zeta potential and transmission electron microscopy. The incorporation efficiency of CORM-2 into FA-CORM-2-SLNs was determined by quantifying ruthenium using ICP-AES. CO release from FA-CORM-2-SLNs were assessed by myoglobin assay. In vitro cytotoxicity of FA-CORM-2-SLNs was evaluated with the MTT assays. In vitro anti-inflammatory effects were evaluated by nitric oxide assay in lipopolysaccharide-stimulated RAW 264.7 macrophages. The targeting ability of FA-CORM-2-SLNs was evaluated by competitive inhibition assay after pretreatment with free folic acid. Results: Spherical FA-CORM-2-SLNs were around 100 nm with narrow particle size distribution. About 90% of CORM-2 was incorporated into FA-CORM-2-SLNs. The sustained CO release from FA-CORM-2-SLNs was observed and the half-life of CO release increased up to 30 times compared with that of CORM-2 solution. Non-cytotoxicity of FA-CORM-2-SLNs was confirmed by evaluating in vitro cell viability of RAW 264.7 macrophages by MTT assay. Through targeting to Raw 264.7 cells, FA-CORM-2-SLNs exhibited better effects than CORM-2-SLNs in NO inhibition, suggesting greater anti-inflammatory activity. Conclusion: Taken together, FA-CORM-2-SLNs have a great potential for targeted CO therapeutics against inflammation via folate receptor-mediated specific delivery.