Polyoxymethylene dimethyl ethers (PODE n, CH 3 O (CH 2 O) n CH 3, where n⩾ 1) are ideal diesel fuel additives. Among the PODE n compounds, PODE 3–5 have the best properties as diesel additives. A theoretical analysis of the molecular size distribution of PODE n synthesized from dimethoxymethane (DMM) and paraformaldehyde (PF) was performed based on a sequential reaction mechanism. The molecular size distribution model follows the Schulz–Flory distribution, and showed a good prediction ability at different reaction temperatures (T) and DMM/CH 2 O mole ratios (M), which verified the sequential reaction mechanism during the formation of PODE n. The product distribution was optimized using the molecular size distribution model and response surface methodology (RSM). At optimum operating conditions of T= 105° C and M= 1.1, the conversion of formaldehyde X CH 2 O has a high value of 92.4%, and the fraction of PODE 3–5 in the PODE n mixture is 33.2 wt%, while the fractions of PODE n> 5 and PODE 2 are 9.4 wt% and 24.3 wt%, respectively.