Exposure and assimilation to a Western environment (acculturation) might impact the health of Asian immigrants to the US. This hypothesis is supported by the lower prevalence of overweight and diabetes in Asians living in Asia compared to those living in the US, but longitudinal studies are lacking. We conducted a longitudinal analysis on 8,634 Asians using data on acculturation (generational status, length of US residence, age at immigration) and BMI history from the California Men's Health Study (2002-2003) and information on repeated, measured BMI and diabetes diagnoses from electronic health records (2005-2012). We determined: (1) differences in BMI changes in Asians living in Asia versus Asians living in the US; (2) the association between acculturation, overweight and BMI change after immigration to the US; and (3) BMI's role as a mediator of the association between acculturation and incident diabetes. We confirmed that Asians living in Asia experienced smaller increases in BMI over time than those living in the US at the same age. After immigration to the US, first-generation, foreign-born Asians gained weight rapidly during their first 25 years in the US, yet they never reached the same level of overweight as their second- and third-generation, US-born counterparts. Contrary to our expectations, Asians born in Asia had a higher risk of diabetes than those born in the US despite their lower BMI levels. Thus, Asians might be exposed to risk factors, other than BMI, prior to migrating to the US. Less acculturated Asians were at even higher diabetes risk when we considered the effect independent of BMI using mediation analysis. Their lower BMI levels protect less acculturated Asian men from diabetes. These results provide novel insights into the influence of a Western environment on BMI and diabetes risk among Asian immigrants and emphasize the importance of public health efforts in this vulnerable ethnic group, which already has elevated diabetes risk at the time of immigration. Interventions focused on maintaining a healthy weight are needed for Asians immediately after immigration to the US.