The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) has gained attention for its pro-inflammatory potential in atherogenesis. This study evaluates LOX-1 receptor modulation in the presence of an atheroprotective cytokine, interleukin-10 (IL-10). Both oxidized low-density lipoprotein (oxLDL) and IL-10 stimulated LOX-1 cell surface expression on THP-1 macrophages. However, our study demonstrates differential roles of oxLDL and IL-10 on LOX-1 functionality. Seemingly, oxLDL-induced LOX-1 promoted pro-inflammatory signalling by increasing intracellular NO, a substrate for pro-inflammatory peroxynitrite. In contrast, IL-10-induced LOX-1 facilitated scavenging of extracellular oxLDL without any effect on pro-inflammatory signalling. The atheroprotective effects of IL-10 were demonstrated by both facilitation of cellular oxLDL uptake and expression of LOXIN, an atheroprotective haplotype of the LOX-1 gene. Thus, increased expression of IL-10 may help to attenuate the risk of atherosclerosis developed by pro-inflammatory signal(s) generated through the interaction of oxLDL with its cognate receptor LOX-1 on macrophages.