Previous studies demonstrated that type I collagen, a major component of the extracellular matrix, could influence the differentiation and function of leukocytes; however, it is not clear whether those effects of collagen were based on its interaction with the classic collagen receptors, alpha1beta1 and alpha2beta1 integrins. We recently detected significant upregulation of discoidin domain receptor 1 (DDR1), a new class of collagen receptor, in human leukocytes, including neutrophils, monocytes, and lymphocytes, in vitro, leading to the hypothesis that the leukocyte-activating effects of collagen might be owing to its interaction with DDR1. In this review, we summarize our recent findings demonstrating that DDR1-collagen interaction facilitates the adhesion, migration, differentiation/maturation, and cytokine/chemokine production of leukocytes. We also describe the intracellular signaling pathways activated by DDR1 interaction with collagen.