Background Assess the effect of clinical-like cryotherapy on inflammatory signs (in vivo neutrophil migration, cytokines and joint inflammation), pain, and joint swelling in mice with knee arthritis. Balance and motor coordination were also evaluated. Methods Young C57BL/6 mice were randomly divided into 3 groups (n = 10/group): control group: animals were not immunized with antigen-induced arthritis (AIA) and no intervention occurred; AIA group: animals immunized with methylated bovine serum albumin (mBSA) for knee arthritis; AIA + cryotherapy group: animals immunized with mBSA and submitted to cryotherapy. After 21days, the study was divided into 6-hour experimental analysis periods after injection-induced joint inflammation with mBSA (100 ug/joint) and a cryotherapy protocol was applied (ice pack, two 20-minute sessions). Number of synovial fluid neutrophils, cytokine levels, joint histology, pain, joint swelling and motor performance were also analyzed. Results Our results showed that the application of cryotherapy in mice with acute knee arthritis reduced inflammatory signs and improved the symptoms of pain and joint swelling, as well as motor coordination and balance in the animals. Conclusions Clinical-like cryotherapy used in the acute phase of arthritis reduced inflammatory signs and improved the symptoms of pain, joint swelling, motor coordination and balance in the mice.