Aim To explore the possible molecular mechanism of low density lipoprotein (LDL) oxidation. Methods Human monocyte line THP-1 cells were induced by natural LDL (100 mg/L) for 0,1, 3 and 5 hours. Induction of monocytes at different time points was for expression profile microarray experiments, and genes related to LDL oxidation were screened. Real-time quantitative PCR and Western blot were used to further validate the results of some microarrays at the levels of mRNA and protein, respectively. Gene clustering, biological functions and signal transduction pathways related to lipid and oxidation were analyzed by using the DAVID database. Results After LDL induced THP-1, the expression of a large number of genes related to biofilm in cells was changed, suggesting that lipid oxidation was localized on biofilm. The expression of lipid oxidation-related genes changed after 3 hours of LDL induction, which imply that lipid oxidation had begun. Functional annotation analysis of differentially expressed genes revealed that Toll-like receptor (TLR) signaling pathway, apoptosis, endocytosis, cell cycle, lipid raft, lipid binding, localization, transport, cell adhesion, metal ion homeostasis, redox and other biological pathways were enriched to varying degrees. The mRNA and protein expressions of inflammatory factors induced by natural LDL were inhibited at different time points in THP-1. For example, the expressions of tumor necrosis factor α, interleukin-33, c-FOS and other genes decreased gradually with the prolongation of incubation time of LDL. Conclusion This study suggests that the oxidation of natural LDL may be related to the recognition and inflammation signal transduction of TLR4-TLR10-CD36.