Our research attempted to address two important questions-how microRNAs modulate atherogenic inflammatory genes from a panoramic viewpoint and whether their augmented expression results from reduced microRNAs suppression. To resolve these knowledge gaps, we employed a novel database mining technique in conjunction with statistical analysis criteria established from experimentally verified microRNAs. We found that the expression of 33 inflammatory genes up-regulated in atherosclerotic lesions contain structural features in the 3′ UTR of their mRNAs for potential microRNAs regulation. Additionally, the binding features governing the interactions between the microRNAs and the inflammatory gene mRNA were statistically identical to the features of experimentally verified microRNAs. Furthermore, 21 (64%) of the 33 inflammatory genes were targeted by highly expressed microRNAs and 10 of these (48%) were targeted by a single microRNA, suggesting microRNA regulation specificity. Supplementing our findings, seven out of the 20 unique microRNAs were previously confirmed to be down-regulated when treated with pro-atherogenic factors. These results indicate a critical role of anti-inflammatory microRNAs in suppressing pro-atherogenic inflammatory gene expression.