Two-point nonuniformity correction (NUC) is the most effective and commonly used algorithm for scientific and commercial infrared imagers. However, conventional two-point NUC requires two references at different levels of flux, which are sometimes difficult to obtain. To overcome this drawback, a neutral-density filter based solution for two-point NUC of cooled infrared focal plane arrays is proposed in this paper. Benefiting from the specially designed filters and an additional concave mirror, NUC can be conducted by using a single reference at ambient temperature. Several experiments were conducted to validate the performance of the proposed NUC method. The results indicate that it yields excellent performance compared with conventional NUC methods; moreover it is more economical and convenient in various applications.