<b><i>Background:</i></b> Idiopathic membranous nephropathy (IMN) has been linked to the lectin pathway, IgG4 and genetic susceptibility. We investigated the frequency of mannose-binding lectin2 (<i>MBL2</i>) gene polymorphisms and the serum ratio of IgG4 in patients with membranous nephropathy (MN). <b><i>Methods:</i></b> Polymorphisms in the exon 1 of the <i>MBL2</i> gene (codons 52, 54, and 57) and single base polymorphisms at positions –550 (HL) and –221 (XY) in the promoter region were evaluated in 60 patients compared to a control group (CG) of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing 2 etiologies of MN: idiopathic (35 patients) and secondary to systemic lupus erythematosus (25 patients). <b><i>Results:</i></b> Patients with MN had a 2.54-fold higher probability (95% CI 1.51–4.31) of carrying the O alelle, exon 1 variant, and 11.16-fold higher probability (95% CI 4.77–28.41) of having A/O genotype when compared to CG. The frequency of polymorphisms in the promoter region was similar between the groups. Combined genotypes generally related to the defective production of MBL (YA/O, XA/O and O/O) were more frequent in patients with MN (OR 7.11; 95% CI 2.69–21.27), when compared to controls. The median of serum ratio IgG4 was 5% for idiopathic MN and 3% for lupus MN patients (<i>p</i> = 0.016). <b><i>Conclusions:</i></b> Our data suggests that <i>MBL2</i> polymorphisms may be associated with the activation of the lectin pathway by IgG4 subclass antibodies in MN.