Objective To investigate the induction effect and mechanism of indoxyl sulfate(IS) on uptake of ox-LDL by RAW264.7 macrophages. Methods RAW264.7 cells were treated with 0, 10, 50, 100, 200 and 400 μmol/L IS for 24 h. CCK-8 assay was employed to obtain the cell survival ratio of RAW264.7 cells, and flow cytometry was employed to detect uptake of ox-LDL by RAW264.7 cells. After RAW264.7 cells were treated with 200 μmol/L IS for 0, 12, 24, 36 and 48 h, and the cell survival ratio and uptake of ox-LDL were obtained. RAW264.7 cells of the IS group were treated with 200 μmol/L IS for 24 h, while the cells of the UO126+IS group were treated with 5 μmol/L UO126 for 2 h in advance and 200 μmol/L IS for 24 h. Then the survival ratio of RAW264.7 cells and uptake of ox-LDL were determined in the non-treated group, IS group and UO126+IS group. And Western blot was used to detect the expression of ERK1/2 protein in the three groups. Results In the detection of dose-dependent effects and time-dependent effects of IS on RAW264.7 cell survival ratio, there was no significant difference between the groups (P > 0.05). Uptake of Dil-ox-LDL positively correlated with the concentration of IS and the action time (P < 0.01). Uptake of Dil-ox-LDL and the expression of p-ERK1/2 of the IS group were greatly higher than those of the non-treatment group (P < 0.01). Uptake of Dil-ox-LDL of the UO126+IS group was slightly lower than that of the non-treatment group, and the difference was no statistically significant (P > 0.05). While the expression of p-ERK1/2 of the UO126+IS group was obviously lower than that of the non-treatment group (P < 0.01). Uptake of Dil-ox-LDL and the expression of p- ERK1/2 of the UO126+IS group were significantly lower than those of the IS group (P < 0.01). Conclusions IS can directly induce uptake of ox-LDL by RAW264. 7 macrophages in vitro through activation of MAPK signaling pathway, and the effect is enhanced with increasing concentration and action time.