Particulate matter (PM) emitted from conventional diesel engines has significant deteriorating effects on natural environment and human health. Among alternative oxygenated fuels, polyoxymethylene dimethyl ether (PODE) is a novel renewable fuel with high cetane number, oxygen content and volatility, and has prominent potential for reducing the PM emissions. In this study, the influences of fuel injection parameters, including injection pressure and injection timing on the reduction of PM emissions were explored for a four-cylinder diesel engine fueled with PODE/diesel blends at various engine loads. The three blends were the pure diesel (denoted as P0), a mixture of 80% diesel and 20% PODE (denoted as PD20), and the mixture of 70% diesel and 30% PODE (denoted as PD30). The results showed that adding PODE to diesel resulted in a reduction in both the total particle number concentration (PNC) and the particle mass concentration (PMC) at all loads. For the PODE/diesel blends, at low load and higher injection pressures, the PMC further decreased, although the value of PNC drastically increased. For the PODE/diesel blends, at medium load and higher injection pressures, both the PNC and PMC values decreased. When the injection pressure was higher than 120 MPa, it could not continuously reduce PNC. Furthermore, for the PODE/diesel blends, at high load and high injection pressures, both the PNC and PMC values greatly decreased. The PODE/diesel blends coupled with the retarded injection timing could reduce the PNC and PMC values, but when the injection timing occurred too close to the top dead center (TDC), the PNC value increased. In addition, as the injection timing was closer to TDC, the effect of the addition of PODE in diesel fuel on reducing PNC and PMC became more significant.