(A) Cohorts of mice were injected i.p daily with saline or metformin (150 mg/kg of body weight) starting one day prior (day −1) to KRN serum transfer and continued daily for the duration of the experiment. On day 0, they were injected i.p. with 175 μl of KRN serum. Changes in arthritis score and ankle thickness were assessed daily. (B) Representative micrographs of day 9 joint sections stained with H&E and toluidine blue. Scale bars = 200 μm (H&E), 50 μm (toluidine blue) (C) Graphical representations of inflammatory cellular infiltrates, bone erosions and cartilage degradation. (D) Day 9 paws were homogenized and cleared lysates were assayed for inflammatory cytokines. Levels are expressed as picograms (pg) per mg of total protein extracts. (E) Arthritis was induced with KRN serum transfer on day 0 and metformin started on day 0 or day 2 after disease is established. Values are presented as mean ± SEM, n = 15 mice in the saline group and 5 mice for each metformin treatment group. *P < 0.05, **P < 0.01, ***P < 0.001