Introduction: Due to increasing request of consumers for non-bovine milks, and to the increase in the number of dairy donkey farms in Italy, farmers require more sophysticated and reliable processing devices, in order to increase their market share beyond local, and to guarantee a safe product of high quality. To this aim, a new small-scale continuous-flow High-Temperature Short-Time (HTST) pasteurizer (72°C for 15 sec), that was initially prototyped by the authors for treating small volumes of human milk, was tested on donkey milk, in order to evaluate its efficacy in producing high quality milk. Materials & Methods: The efficacy of the new HTST device on raw donkey milk microflora was tested by Total Aerobic Bacteria, Enterobacteriaceae and Bacillus cereus enumeration. In addition, the biochemical quality of donkey milk after HTST pasteurization was assessed by determining the protein profile in both reducing and non reducing conditions and by measuring lysozyme activity, and compared to that achieved by standard Holder pasteurization (63°C for 30 min). Results and Discussion: The new HTST apparatus was shown to be able to reduce the total bacteria count to undetectable level, as well as to completely eradicate Enterobacteriaceae. Bacillus cereus, when present, was eradicated with variable efficiency, mainly depending on the bacterial loads of the starting raw milk. Changes in the protein profile were observed in the milk pasteurized according to both processes. In detail, HTST seems to preserve the protein profile more than the traditional Holder method, limiting casein degradation. Nevertheless, both methods reduced significantly lysozyme activity with respect to raw donkey milk, thus indicating that structural changes may occurr also in less intense methods. In conclusion, the HTST method should be applied to safely pasteurize donkey milk, despite the low volumes involved in the standard routine of small dairy donkey farms. Moreover, this new device could represent an interesting strategy to ensure a higher retention of some protein fractions. Further evaluations and efficient device prototypation could thus contribute to both consumer safety, in particular for baby nutrition, and to increase of farmers' market consistency.