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Campaign in the Levant and Syria

Thutmose's Tombos stele indicates that he had already fought a campaign in Syria; hence, his Syrian campaign may be placed at the beginning of his second regnal year. This second campaign was the farthest north any Egyptian ruler had ever campaigned.

Although it has not been found in modern times, he apparently set up a stele when he crossed the Euphrates River. During this campaign, the Syrian princes declared allegiance to Thutmose. But after he returned, they discontinued tribute and began fortifying against future incursions. Thutmose celebrated his victories with an elephant hunt in the area of Niy, near Apamea in Syria, and returned to Egypt with strange tales of the Euphrates, "that inverted water which flows upstream when it ought to be flowing downstream." The Euphrates was the first major river the Egyptians had ever encountered that flowed from the north, which was downstream on the Nile, to the south, upstream on the Nile. Thus the river became known in Egypt as simply "inverted water."

Textual sources from the time of Thutmose I include references to Retenu, Naharin, and the 'land of Mitanni '. The last is believed to be the first historical reference to that kingdom.

Many Levantine sites were destroyed in the middle of the 16th century B.C., and these destructions have often been attributed to the military campaigns of Thutmose I, or of his predecessor Amenhotep I. Initially these campaigns may have aimed at defeating the power of the Hyksos, who were formerly strong in this area.

As many as 20 sites in the Levant suffered destruction at this time. For example, the fiery destruction of Stratum XVIII at Gezer has been assigned to the second half of the 16th century BCE, the time of Amenhotep I and Thutmose I, based on the pottery and scarabs discovered in the destruction debris.

It does not appear that the Egyptians' aim at this stage was to control the area permanently, because they established no permanent presence in the area. This happened later, during the 18th dynasty.