Monocyte chemoattractant protein-1 (MCP-1) and its receptor CC-chemokine receptor-2 (CCR2) have been implicated in inflammatory disease pathologies such as rheumatoid arthritis, multiple sclerosis, Crohn's Disease, uveitis, diabetes and diabetic complications, allergic rhinitis, Chronic Obstructive Pulmonary Disease (COPD) and allergic asthma. There remains a need for small molecule CCR2 antagonists for preventing, treating or ameliorating a CCR2-mediated inflammatory syndrome, disorder or disease resulting from MCP-1 induced monocyte and lymphocyte migration to a site of inflammation. We have discovered a series of substituted dipiperidine acids and alcohols as selective CCR2 antagonists. Exploratory SAR studies led to the remarkably potent CCR2 antagonists displaying excellent binding affinity and functional antagonism with values in the nanomolar or picomolar range. Some of compounds showed excellent efficacy in adjuvant-induced arthritis model, collagen-induced arthritis model, and allergic asthma model. The detail SAR, in vitro and in vivo activities will be discussed.