Objective: To investigate the correlation between serum galectin-3 (Gal-3) level and disease activity or pathological activity index of lupus nephritis (LN). Methods: A total of 83 patients with lupus nephritis treated in our hospital were enrolled, including 42 active LN patients, and 41 stable LN patients. The other 40 healthy subjects were as healthy controls. Fasting peripheral blood was collected from the subjects, and serum levels of Gal-3, anti-double-stranded DNA (ds-DNA) antibody, complement 3 (C3), tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were detected by ELISA, and the correlations between serum Gal-3 level and activity index (AI), serum TNF-α or IL-1β were analyzed. Renal biopsy tissue was collected, and the expression of Gal-3 in the renal tissue of subjects was measured by Western blotting and immunohistochemistry, and the distribution of Gal-3 and renal tissue macrophages in renal tissues was detected by immunofluorescence. Results: Compared with healthy subjects, serum levels of Gal-3, TNF-α, and IL-1β were significantly higher in LN patients, and the levels of these factors were significantly higher in active LN patients than those in stable LN patients (P<0.05). Serum Gal-3 level was positively correlated with AI, anti-ds-DNA antibody, TNF-α, IL-1β, and negatively correlated with complement C3, respectively. The levels of Gal-3 expression in the renal tissues of patients with active LN were significantly higher than those in patients with stable LN. Conclusion: A positive correlation between serum Gal-3 and LN pathological activity index in active LN patients, suggesting that Gal-3 may mediate LN development by regulating inflammatory response.