Abstract: Objective To investigate the correlation of apolipoprotein AI (ApoAI), ApoB , ApoB/ApoAI and the severity of brain white matter lesions (WML). Methods A total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (n=386) and moderate to severe WML group (n=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML. Results Univariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups (P<0.05), but ApoB levels were similar between them (P>0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95%CI: 3.622-36.229, P< 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95%CI: 0.018-0.262, P<0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML (P<0.001). Conclusion An increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.