The degree of tissue injuries such as the level of scarring or organ dysfunction, and the immune response against them primarily determine the outcome and speed of healing process. The successful regeneration of functional tissues requires proper modulation of inflammation-producing immune cells and bioactive factors existing in the damaged microenvironment. In the tissue repair and regeneration processes, different types of biomaterials are implanted either alone or by combined with other bioactive factors, which will interact with the immune systems including immune cells, cytokines and chemokines etc. to achieve different results highly depending on this interplay. In this review article, the influences of different types of biomaterials such as nanoparticles, hydrogels and scaffolds on the immune cells and the modification of immune-responsive factors such as reactive oxygen species (ROS), cytokines, chemokines, enzymes, and metalloproteinases in tissue microenvironment are summarized. In addition, the recent advances of immune-responsive biomaterials in therapy of inflammation-associated diseases such as myocardial infarction, spinal cord injury, rheumatoid arthritis, inflammatory bowel disease and diabetic ulcer are discussed.